The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes

J Clin Endocrinol Metab. 2002 Mar;87(3):1282-90. doi: 10.1210/jcem.87.3.8337.


Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol x kg(-1) x min(-1)) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / blood*
  • Exenatide
  • Female
  • Glucose Clamp Technique
  • Half-Life
  • Humans
  • Insulin / blood*
  • Male
  • Middle Aged
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Postprandial Period
  • Reference Values
  • Venoms*


  • Blood Glucose
  • Insulin
  • Peptides
  • Venoms
  • Exenatide